Introduction
Uplizna (inebilizumab-cdon) is a humanized monoclonal antibody approved by the FDA for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive. It represents a significant advancement in the management of this rare autoimmune disorder that primarily affects the optic nerves and spinal cord.
Mechanism of Action
Uplizna targets and depletes CD19-positive B cells through antibody-dependent cellular cytotoxicity. Unlike other B-cell-depleting therapies that target CD20, Uplizna's unique mechanism affects a broader range of B-lineage cells, including plasmablasts and some plasma cells. This action reduces the production of pathogenic autoantibodies, including AQP4-IgG antibodies, which are central to the pathophysiology of NMOSD.
Indications
- Treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive
Dosage and Administration
Initial dose: 300 mg intravenous infusion administered at baseline and again two weeks later Maintenance dose: 300 mg intravenous infusion every 6 months Administration:- Administer as an intravenous infusion over approximately 90 minutes
- Pre-medicate with methylprednisolone 100 mg IV (or equivalent) approximately 30 minutes before infusion
- Pre-medicate with an antihistamine (e.g., diphenhydramine) approximately 30-60 minutes before infusion
- Pre-medicate with an antipyretic (e.g., acetaminophen) approximately 30-60 minutes before infusion
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Not studied
- Geriatric patients: No specific dosage adjustment recommended
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Volume of distribution approximately 3.9 L Metabolism: Degraded via proteolytic enzymes throughout the body Elimination: Half-life approximately 18 days Time to maximum concentration: Immediately following infusion completionContraindications
- History of life-threatening infusion reaction to Uplizna
- Active hepatitis B virus infection
- Active or untreated latent tuberculosis
Warnings and Precautions
Infusion Reactions: May occur during and up to 24 hours after infusion. Monitor patients closely during infusion and have appropriate medical support available. Infections: Increased risk of infections, including opportunistic infections. Screen for tuberculosis and hepatitis B before initiation. Reduction in Immunoglobulins: Monitor immunoglobulin levels during treatment. Fetal Risk: Based on animal data, may cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after last dose. Vaccinations: Administer all age-appropriate vaccinations according to immunization guidelines before initiating treatment. Live-attenuated or live vaccines are not recommended during treatment.Drug Interactions
- Immunosuppressive therapies: May increase risk of infections
- Live vaccines: Avoid concomitant administration
- B-cell depleting therapies: Avoid concomitant use
Adverse Effects
Most common adverse reactions (≥10%):- Urinary tract infection
- Arthralgia
- Fatigue
- Nausea
- Headache
- Back pain
- Dizziness
- Pharyngitis
- Pain in extremity
- Insomnia
- Infusion reaction
- Gastroenteritis
- Upper respiratory tract infection
- Anxiety
- Blurred vision
- Diarrhea
- Rash
- Influenza
- Neutropenia
- Infections
- Infusion reactions
Monitoring Parameters
Before initiation:- Quantitative serum immunoglobulins
- Hepatitis B virus screening
- Tuberculosis screening
- Complete blood count with differential
- Pregnancy test for females of reproductive potential
- Monitor for signs of infusion reactions during and for at least 1 hour after completion
- Monitor for signs and symptoms of infections
- Periodic monitoring of immunoglobulins
- Monitor complete blood count periodically
- Regular assessment of neurological status
- Ophthalmologic examinations as clinically indicated
- MRI monitoring as clinically indicated
Patient Education
- Report any signs of infection (fever, chills, cough, sore throat) immediately
- Understand the importance of completing all recommended vaccinations before starting treatment
- Be aware of potential infusion reactions and report any symptoms during or after infusion
- Use effective contraception during treatment and for 6 months after last dose if of reproductive potential
- Inform all healthcare providers about Uplizna treatment before any vaccinations or new medications
- Keep all scheduled infusion appointments and follow-up visits
- Report any new neurological symptoms or vision changes promptly
References
1. Cree BAC, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019;394(10106):1352-1363. 2. Uplizna [package insert]. Boston, MA: Horizon Therapeutics; 2020. 3. Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of inebilizumab in neuromyelitis optica spectrum disorder: results of the N-MOmentum study. Neurology. 2020;94(15 Supplement):S42.001. 4. National Multiple Sclerosis Society. NMOSD Treatments. 2021. 5. FDA Approval Letter: Uplizna (inebilizumab-cdon). June 11, 2020.